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Pharmacological Study of A3 Adenosine Receptor agonist (AB Meca) in Xenograft Lung Cancer Model in Mice through In Silico and In Vivo Approach: Targeting TNF-α

Author(s):

Nilay Solanki*, Leena Patel, Shaini Shah , Ashish Patel , Swayamprakash Patel, Mehul Patel and Umang Shah   Pages 1 - 8 ( 8 )

Abstract:


Background: Lung cancer is the leading cause of mortality in India. Adenosine Receptor (AR) has emerged as a novel cancer-specific target. A3AR levels are upregulated in various tumor cells, which may mean that the specific AR may act as a biological marker and target specific ligands leading to cell growth inhibition.

Aim: Our aim was to study the efficacy of the adenosine receptor agonist, AB MECA, by in silico (molecular docking) and in vitro (human cancer cells in xenografted mice) studies.

Methods: Molecular docking on the AB-meca and TNF-α was performed using AutoDock. A549 Human lung cancer 2 ×106 cells per microliter per mouse injected via intrabronchial route. Rat TNF-α level was assessed by ELISA method.

Results: AB Meca's predicted binding energy (beng) with TNF-α was 97.13 kcal/mol, and the compatible docking result of a small molecular inhibitor with TNF-α native ligand beng was 85.76 kcal/mol. In vivo, a single dose of lung cancer cell A549 is being researched to potentiate tumor development. Doxorubicin and A3AR agonist therapies have lowered TNF-alpha levels that were associated with in silico function. The A3AR Agonist showed myeloprotective effects in the groups treated along with doxorubicin.

Conclusion: AB MECA’s higher binding energy (beng) with TNF-α mediated reduction of tumor growth in our lung cancer in vivo model suggested that it may be an effective therapy for lung cancer.

Keywords:

Molecular docking, lung cancer, A3 adenosine receptor agonist, TNF- α, doxorubicin, adenosine receptor.

Affiliation:

Ramanbhai Patel College of Pharmacy, Charotar University of Science and Technology, Changa, Gujarat, CBCC Global Research Pvt Ltd, Ahmadabad, Gujarat, Ramanbhai Patel College of Pharmacy, Charotar University of Science and Technology, Changa, Gujarat, Ramanbhai Patel College of Pharmacy, Charotar University of Science and Technology, Changa, Gujarat, Ramanbhai Patel College of Pharmacy, Charotar University of Science and Technology, Changa, Gujarat, Ramanbhai Patel College of Pharmacy, Charotar University of Science and Technology, Changa, Gujarat, Ramanbhai Patel College of Pharmacy, Charotar University of Science and Technology, Changa, Gujarat



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